Toxopain-1 is critical for infection in a novel chicken embryo model of congenital toxoplasmosis
Toxopain-1 is critical for infection in a novel chicken embryo model of congenital toxoplasmosis
复制标题
DOI：
10.1128/iai.72.5.2915-2921.2004
复制
发表时间：
2004-05-01
影响因子：
3.1
通讯作者：
Reed, SL
中科院分区：
文献类型：
--
作者：
Que, XC;Wunderlich, A;Reed, SL
我们检验了组织蛋白酶，特别是组织蛋白酶B-toxopain-1在弓形虫病发病机制中起关键作用的假设。我们发现，抑制toxopain-1特异性mRNA和蛋白质的表达>60%显著降低了寄生虫体外繁殖和入侵的能力。为了将这些体外结果与弓形虫蛋白酶-1在体内发病机制中的作用联系起来，我们开发了一种新的先天性弓形虫病鸡胚模型。抑制toxopain-1的表达或特异性半胱氨酸蛋白酶活性显着降低先天性感染的鸡胚，所确定的组织病理学和定量的寄生虫的数量通过实时PCR。我们的新模型提供了关键的体内验证的假设，即toxopain-1是一个潜在的药物靶点在弓形虫，也提供了一个新的动物模型，快速，廉价的抗寄生虫化合物的筛选。
We tested the hypothesis that cathepsins and specifically toxopain-1, a cathepsin B, play a critical role in the pathogenesis of toxoplasmosis. We found that inhibiting the expression of toxopain-1-specific mRNA and protein by >60% significantly decreased the capacity of the parasites to multiply and invade in vitro. To relate these in vitro results to the role of toxopain-1 in pathogenesis in vivo, we developed a novel chicken embryo model of congenital toxoplasmosis. Inhibiting either toxopain-1 expression or specific cysteine proteinase activity significantly reduced congenital infection of chicken embryos, as determined by histopathology and by the number of parasites quantified by real-time PCR. Our new model provides key in vivo validation for the hypothesis that toxopain-1 is a potential drug target in Toxoplasma gondii and also provides a new animal model for rapid, inexpensive screening of antiparasitic compounds.